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2 Chapter 9 Major Histocompatibility ComplexContentsPartⅠ Several important conceptsPartⅡ Composition of HLA complexPartⅢ Genetic characteristics of HLAPartⅣ Molecular structure and distribution of HLAPartⅤ Interaction of MHC molecules and antigen peptidePartⅥ Biological functions of MHCPartⅦ Application of HLA in medicine

3 PartⅠ Several important conceptsTransplantation antigen(Histocompatibility antigen): Antigens which cause immune response to the graft and determine the survival of the graft.They are alloantigen which is specific for each individual.

4 MHS(Major histocompatibility antigen system )：A group of complex histocompatibility antigens which cause rapid and strong immunoreaction to the graft.mHS(Minor histocompatibility antigen system)：A group of complex histocompatibility antigens which cause slow and weak immunoreaction to the graft.

5 MHC (Major histocompatibility complex)：A large cluster of linked genes located in some chromosome of human or other mammals encode for MHS and relate to allograft rejection, immune response, immune regulation and cell-cell recognition.

21 2. PolymorphismPolymorphism means there are multiple alleles at a gene locus of MHC in a population so that an individual may have variant allele.------multiple allele------codominance: The two alleles at a gene locus of MHC in the two homogenous chromosomes are expressed together.

24 3. Linkage disequilibriumThe distribution of haplotypes is not random in a population.The probability in which two or more than two alleles present together in one chromosome is greater than the probability in which they present randomly.

29 (4) Function of each domain1 and 2 domains: Interact to form a peptide-binding region which is a groove(cleft) having a "floor"of 8 beta-pleated strands and two "walls" with alpha-helices.( Containing a peptide of aa in the groove)

36 (5) Function of each domainα1 and 1: Interact to form the peptide-binding region which is a groove having a "floor" of 8 beta-pleated strands and two "walls" with alpha-helices.(Containing a peptide of 10-30aa in the groove)

43 Interaction between MHC and antigenAnchor sites: Two or more sites on antigenic peptide bind to “groove” or “pocket” of MHC molecules.Anchor residues: The amino acid residues on anchor sites of antigenic peptide.

44 Antigenic peptides which can combine with Interaction between MHC and antigenCertain MHC molecule binds the corresponding anchor residue of antigenic peptides.Antigenic peptides which can combine withthe same kind of MHC molecule have same or similar anchor sites and anchor residues(consensus motif).

58 MLRMixed lymphocyte reaction to determine identity of class II HLA antigens between a potential donor and recipient.Lymphocytes from the donor are irradiated or treated with mitomycin C. If the class II antigens on the two cell populations are different, the recipient cells will divide rapidly and take up large quantities of radioactive nucleotides into the newly synthesized nuclear DNA. The amount of radioactive nucleotide uptake is roughly proportionate to the MHC class II differences between the donor and recipient lymphocytes.